11-4094744-C-T

Variant names:

• chr11-4094744-C-T
• rs12806698
• ENST00000532710.5:n.38C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000532710.5(RRM1):​n.38C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RRM1 ENST00000532710.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795
• Publications: 54 publications found

Genes affected

RRM1 (HGNC:10451): (ribonucleotide reductase catalytic subunit M1) This gene encodes the large and catalytic subunit of ribonucleotide reductase, an enzyme essential for the conversion of ribonucleotides into deoxyribonucleotides. A pool of available deoxyribonucleotides is important for DNA replication during S phase of the cell cycle as well as multiple DNA repair processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

RRM1 Gene-Disease associations (from GenCC):

• progressive external ophthalmoplegia with mitochondrial DNA deletions

  Inheritance: AR, AD Classification: LIMITED Submitted by: Ambry Genetics
• progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6

  Inheritance: AR, AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRM1	NM_001318064.1	c.-382C>T		5_prime_UTR_variant	Exon 1 of 18		NP_001304993.1
RRM1	NM_001033.5	c.-269C>T		upstream_gene_variant		ENST00000300738.10	NP_001024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRM1	ENST00000300738.10	c.-269C>T		upstream_gene_variant		1	NM_001033.5	ENSP00000300738.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 413596 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 216512

African (AFR) AF: 0.00 AC: 0 AN: 11904

American (AMR) AF: 0.00 AC: 0 AN: 17644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12986

East Asian (EAS) AF: 0.00 AC: 0 AN: 29828

South Asian (SAS) AF: 0.00 AC: 0 AN: 41726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1796

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 246098

Other (OTH) AF: 0.00 AC: 0 AN: 24134

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.5
DANN	Benign	0.81
PhyloP100		-0.80
PromoterAI		-0.034	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12806698; hg19: chr11-4115974;